Cochlear Duct
Organ of Corti
Ear, Inner
Stria Vascularis
Cochlea
Endolymphatic Duct
Hair Cells, Auditory
Gene Expression Regulation, Developmental
Bile Ducts
Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness. (1/43)
DFN3, an X chromosome-linked nonsyndromic mixed deafness, is caused by mutations in the BRN-4 gene, which encodes a POU transcription factor. Brn-4-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a dramatic reduction in endocochlear potential. Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. The findings suggest that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function. (+info)Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. (2/43)
BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems. (+info)Spiral ligament pathology: a major aspect of age-related cochlear degeneration in C57BL/6 mice. (3/43)
Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hair cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded from base to apex with increasing age, and loss of cochlear neurons was consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain. (+info)Transcript profiling of functionally related groups of genes during conditional differentiation of a mammalian cochlear hair cell line. (4/43)
We have used Affymetrix high-density gene arrays to generate a temporal profile of gene expression during differentiation of UB/OC-1, a conditionally immortal cell line derived from the mouse cochlea. Gene expression was assessed daily for 14 days under differentiating conditions. The experiment was replicated in two separate populations of cells. Profiles for selected genes were correlated with those obtained by RT-PCR, TaqMan analysis, immunoblotting, and immunofluorescence. The results suggest that UB/OC-1 is derived from a population of nonsensory epithelial cells in the greater epithelial ridge that have the potential to differentiate into a hair-cell-like phenotype, without the intervention of Math1. Elements of the Notch signaling cascade were identified, including the receptor Notch3, with a transient up-regulation that suggests a role in hair cell differentiation. Several genes showed a profile similar to Notch3, including the transcriptional co-repressor Groucho1. UB/OC-1 also expressed Me1, a putative partner of Math1 that may confer competence to differentiate into hair cells. Cluster analysis revealed expression profiles for neural guidance genes associated with Gata3. The temporal dimension of this analysis provides a powerful tool to study genetic mechanisms that underlie the conversion of nonsensory epithelial cells into hair cells. (+info)Forced activation of Wnt signaling alters morphogenesis and sensory organ identity in the chicken inner ear. (5/43)
Components of the Wnt signaling pathway are expressed in the developing inner ear. To explore their role in ear patterning, we used retroviral gene transfer to force the expression of an activated form of beta-catenin that should constitutively activate targets of the canonical Wnt signaling pathway. At embryonic day 9 (E9) and beyond, morphological defects were apparent in the otic capsule and the membranous labyrinth, including ectopic and fused sensory patches. Most notably, the basilar papilla, an auditory organ, contained infected sensory patches with a vestibular phenotype. Vestibular identity was based on: (1) stereociliary bundle morphology; (2) spacing of hair cells and supporting cells; (3) the presence of otoliths; (4) immunolabeling indicative of vestibular supporting cells; and (5) expression of Msx1, a marker of certain vestibular sensory organs. Retrovirus-mediated misexpression of Wnt3a also gave rise to ectopic vestibular patches in the cochlear duct. In situ hybridization revealed that genes for three Frizzled receptors, c-Fz1, c-Fz7, and c-Fz10, are expressed in and adjacent to sensory primordia, while Wnt4 is expressed in adjacent, nonsensory regions of the cochlear duct. We hypothesize that Wnt/beta-catenin signaling specifies otic epithelium as macular and helps to define and maintain sensory/nonsensory boundaries in the cochlear duct. (+info)Distribution of gentamicin in the guinea pig inner ear after local or systemic application. (6/43)
Uptake and retention of gentamicin by cells in the guinea pig inner ear after a single peritoneal injection or local application on the round window were investigated using immunocytochemistry to localize the drug. The cells that accumulated the drug under the two conditions were the same, but staining for the drug was more intense and was often accompanied by widespread cochlear degeneration following local application. Soon after drug administration by either route, there was diffuse staining for the drug throughout all tissue within the labyrinth, including bone. At later times when distinct cell staining became evident, virtually all cell types were found to be positive, with several cell types staining more darkly for the drug than hair cells, indicating that hair cells were not the most avid in accumulating gentamicin. The infracuticular portion of auditory and vestibular hair cells as well as type III fibrocytes of the spiral ligament were positively stained in almost all cases and these sites were found to be positive for as long as six months post administration. In animals with loss of the organ of Corti, there was unusually intense staining for gentamicin in root cells of the spiral ligament, in marginal cells of the stria vascularis, and in cells of the spiral limbus. Dark staining of surviving cells in cases with overt tissue destruction suggests that variability in the extent of damage caused by the drug was determined more by the degree of its local uptake than by differences in animals' capacities to metabolize the drug systemically. The present results show that gentamicin may damage or destroy all cochlear cells following a single round window application. The findings broaden the scope of our knowledge of cochlear gentamicin uptake and damage and have implications for treatment of patients with vestibular disorders by infusion of aminoglycosides into the middle ear, as well as implications for prospects of rehabilitating patients that have been deafened by aminoglycosides. (+info)Changes in cytochemistry of sensory and nonsensory cells in gentamicin-treated cochleas. (7/43)
Effects of a single local dose of gentamicin upon sensory and nonsensory cells throughout the cochlea were assessed by changes in immunostaining patterns for a broad array of functionally important proteins. Cytochemical changes in hair cells, spiral ganglion cells, and cells of the stria vascularis, spiral ligament, and spiral limbus were found beginning 4 days post administration. The extent of changes in immunostaining varied with survival time and with cell type and was not always commensurate with the degree to which individual cell types accumulated gentamicin. Outer hair cells, types I and II fibrocytes of the spiral ligament, and fibrocytes in the spiral limbus showed marked decreases in immunostaining for a number of constituents. In contrast, inner hair cells, type III fibrocytes and root cells of the spiral ligament, cells of the stria vascularis, and interdental cells in the spiral limbus showed less dramatic decreases, and in some cases they showed increases in immunostaining. Results indicate that, in addition to damaging sensory cells, local application of gentamicin results in widespread and disparate disruptions of a variety of cochlear cell types. Only in the case of ganglion cells was it apparent that the changes in nonsensory cells were secondary to loss or damage of hair cells. These results indicate that malfunction of the ear following gentamicin treatment is widespread and far more complex than simple loss of sensory elements. The results have implications for efforts directed toward detecting, preventing, and treating toxic effects of aminoglycosides upon the inner ear. (+info)Synchronization of a nonlinear oscillator: processing the cf component of the echo-response signal in the cochlea of the mustached bat. (8/43)
Cochlear microphonic potential (CM) was recorded from the CF2 region and the sparsely innervated zone (the mustached bat's cochlea fovea) that is specialized for analyzing the Doppler-shifted echoes of the first-harmonic (approximately 61 kHz) of the constant-frequency component of the echolocation call. Temporal analysis of the CM, which is tuned sharply to the 61 kHz cochlear resonance, revealed that at the resonance frequency, and within 1 msec of tone onset, CM is broadly tuned with linear magnitude level functions. CM measured during the ongoing tone and in the ringing after tone offset is 50 dB more sensitive, is sharply tuned, has compressive level functions, and the phase leads onset CM by 90 degrees: an indication that cochlear responses are amplified during maximum basilar membrane velocity. For high-level tones above the resonance frequency, CM appears at tone onset and after tone offset. Measurements indicate that the two oscillators responsible for the cochlear resonance, presumably the basilar and tectorial membranes, move together in phase during the ongoing tone, thereby minimizing net shear between them and hair cell excitation. For tones within 2 kHz of the cochlear resonance the frequency of CM measured within 2 msec of tone onset is not that of the stimulus but is proportional to it. For tones just below the cochlear resonance region CM frequency is a constant amount below that of the stimulus depending on CM measurement delay from tone onset. The frequency responses of the CM recorded from the cochlear fovea can be accounted for through synchronization between the nonlinear oscillators responsible for the cochlear resonance and the stimulus tone. (+info)The cochlear duct, also known as the scala media, is a membranous duct located within the cochlea of the inner ear. It is one of three fluid-filled compartments in the cochlea, along with the vestibular duct (scala vestibuli) and the tympanic duct (scala tympani).
The cochlear duct contains endolymph, a specialized fluid that carries electrical signals to the auditory nerve. The organ of Corti, which is responsible for converting sound vibrations into electrical signals, is located within the cochlear duct.
The cochlear duct runs along the length of the cochlea and is separated from the vestibular duct by Reissner's membrane and from the tympanic duct by the basilar membrane. These membranes help to create a highly sensitive and selective environment for sound perception, allowing us to hear and distinguish different frequencies and intensities of sound.
The Organ of Corti is the sensory organ of hearing within the cochlea of the inner ear. It is a structure in the inner spiral sulcus of the cochlear duct and is responsible for converting sound vibrations into electrical signals that are sent to the brain via the auditory nerve.
The Organ of Corti consists of hair cells, which are sensory receptors with hair-like projections called stereocilia on their apical surfaces. These stereocilia are embedded in a gelatinous matrix and are arranged in rows of different heights. When sound vibrations cause the fluid in the cochlea to move, the stereocilia bend, which opens ion channels and triggers nerve impulses that are sent to the brain.
Damage or loss of hair cells in the Organ of Corti can result in hearing loss, making it a critical structure for maintaining normal auditory function.
The inner ear is the innermost part of the ear that contains the sensory organs for hearing and balance. It consists of a complex system of fluid-filled tubes and sacs called the vestibular system, which is responsible for maintaining balance and spatial orientation, and the cochlea, a spiral-shaped organ that converts sound vibrations into electrical signals that are sent to the brain.
The inner ear is located deep within the temporal bone of the skull and is protected by a bony labyrinth. The vestibular system includes the semicircular canals, which detect rotational movements of the head, and the otolith organs (the saccule and utricle), which detect linear acceleration and gravity.
Damage to the inner ear can result in hearing loss, tinnitus (ringing in the ears), vertigo (a spinning sensation), and balance problems.
Stria vascularis is a highly vascularized (rich in blood vessels) structure located in the cochlea of the inner ear. It plays a crucial role in the process of hearing by maintaining the endocochlear potential, which is essential for the conversion of sound waves into electrical signals that can be interpreted by the brain. The stria vascularis is composed of three layers: the marginal cells, intermediate cells, and basal cells, which work together to maintain the ionic balance and generate the endocochlear potential. Damage to the stria vascularis can result in hearing loss.
The cochlea is a part of the inner ear that is responsible for hearing. It is a spiral-shaped structure that looks like a snail shell and is filled with fluid. The cochlea contains hair cells, which are specialized sensory cells that convert sound vibrations into electrical signals that are sent to the brain.
The cochlea has three main parts: the vestibular canal, the tympanic canal, and the cochlear duct. Sound waves enter the inner ear and cause the fluid in the cochlea to move, which in turn causes the hair cells to bend. This bending motion stimulates the hair cells to generate electrical signals that are sent to the brain via the auditory nerve.
The brain then interprets these signals as sound, allowing us to hear and understand speech, music, and other sounds in our environment. Damage to the hair cells or other structures in the cochlea can lead to hearing loss or deafness.
The endolymphatic duct is a narrow canal in the inner ear that is part of the membranous labyrinth. It connects the utricle and saccule (two sensory structures in the vestibular system responsible for detecting changes in head position and movement) to the endolymphatic sac (a dilated portion of the duct that helps regulate the volume and pressure of endolymph, a fluid found within the membranous labyrinth).
The endolymphatic duct plays a crucial role in maintaining the balance and homeostasis of the inner ear by allowing the absorption and circulation of endolymph. Disorders or abnormalities in this region can lead to various vestibular and hearing dysfunctions, such as Meniere's disease, endolymphatic hydrops, and other inner ear disorders.
Auditory hair cells are specialized sensory receptor cells located in the inner ear, more specifically in the organ of Corti within the cochlea. They play a crucial role in hearing by converting sound vibrations into electrical signals that can be interpreted by the brain.
These hair cells have hair-like projections called stereocilia on their apical surface, which are embedded in a gelatinous matrix. When sound waves reach the inner ear, they cause the fluid within the cochlea to move, which in turn causes the stereocilia to bend. This bending motion opens ion channels at the tips of the stereocilia, allowing positively charged ions (such as potassium) to flow into the hair cells and trigger a receptor potential.
The receptor potential then leads to the release of neurotransmitters at the base of the hair cells, which activate afferent nerve fibers that synapse with these cells. The electrical signals generated by this process are transmitted to the brain via the auditory nerve, where they are interpreted as sound.
There are two types of auditory hair cells: inner hair cells and outer hair cells. Inner hair cells are the primary sensory receptors responsible for transmitting information about sound to the brain. They make direct contact with afferent nerve fibers and are more sensitive to mechanical stimulation than outer hair cells.
Outer hair cells, on the other hand, are involved in amplifying and fine-tuning the mechanical response of the inner ear to sound. They have a unique ability to contract and relax in response to electrical signals, which allows them to adjust the stiffness of their stereocilia and enhance the sensitivity of the cochlea to different frequencies.
Damage or loss of auditory hair cells can lead to hearing impairment or deafness, as these cells cannot regenerate spontaneously in mammals. Therefore, understanding the structure and function of hair cells is essential for developing therapies aimed at treating hearing disorders.
Developmental gene expression regulation refers to the processes that control the activation or repression of specific genes during embryonic and fetal development. These regulatory mechanisms ensure that genes are expressed at the right time, in the right cells, and at appropriate levels to guide proper growth, differentiation, and morphogenesis of an organism.
Developmental gene expression regulation is a complex and dynamic process involving various molecular players, such as transcription factors, chromatin modifiers, non-coding RNAs, and signaling molecules. These regulators can interact with cis-regulatory elements, like enhancers and promoters, to fine-tune the spatiotemporal patterns of gene expression during development.
Dysregulation of developmental gene expression can lead to various congenital disorders and developmental abnormalities. Therefore, understanding the principles and mechanisms governing developmental gene expression regulation is crucial for uncovering the etiology of developmental diseases and devising potential therapeutic strategies.
Bile ducts are tubular structures that carry bile from the liver to the gallbladder for storage or directly to the small intestine to aid in digestion. There are two types of bile ducts: intrahepatic and extrahepatic. Intrahepatic bile ducts are located within the liver and drain bile from liver cells, while extrahepatic bile ducts are outside the liver and include the common hepatic duct, cystic duct, and common bile duct. These ducts can become obstructed or inflamed, leading to various medical conditions such as cholestasis, cholecystitis, and gallstones.
The pancreatic ducts are a set of tubular structures within the pancreas that play a crucial role in the digestive system. The main pancreatic duct, also known as the duct of Wirsung, is responsible for transporting pancreatic enzymes and bicarbonate-rich fluid from the pancreas to the duodenum, which is the first part of the small intestine.
The exocrine portion of the pancreas contains numerous smaller ducts called interlobular ducts and intralobular ducts that merge and ultimately join the main pancreatic duct. This system ensures that the digestive enzymes and fluids produced by the pancreas are effectively delivered to the small intestine, where they aid in the breakdown and absorption of nutrients from food.
In addition to the main pancreatic duct, there is an accessory pancreatic duct, also known as Santorini's duct, which can sometimes join the common bile duct before emptying into the duodenum through a shared opening called the ampulla of Vater. However, in most individuals, the accessory pancreatic duct usually drains into the main pancreatic duct before entering the duodenum.